Hepatitis C virus genotype 3a with phylogenetically distinct origin is circulating in Pakistan
© Rehman et al; licensee BioMed Central Ltd. 2011
Received: 5 December 2010
Accepted: 6 January 2011
Published: 6 January 2011
Hepatitis C virus (HCV) is one of the leading causes of viral hepatitis worldwide and its genotype 3a is predominant in vast areas of Pakistan.
The present study reports the first full sequence of HCV 3a isolate PK-1 from Pakistan. This nucleotide sequence was compared with six other HCV genotype 3a full length sequences from different regions of the world by using statistical methods of phylogenetic analysis.
The nucleotide difference of these seven sequences shows that HCV genotype 3a of phylogenetically distinct origin is circulating in Pakistan.
Hepatitis C virus (HCV) is leading cause of chronic liver disease  with estimated 170-200 million infected persons worldwide  including approximately 17 million in Pakistan . It is positive single stranded RNA virus first isolated in 1819 and is a member of Flaviviridae [2, 4]. The HCV genome is about 9.6 kb in length consisting of single open reading frame encoding a polyprotein of 3,000 amino acids and non-translated regions located at the 5'and 3' terminus .
The relative prevalence of HCV genotypes varies with the geographic area but genotypes 1, 2 and 3 have worldwide distribution. 1a and 1b are the most widespread genotypes in the Europe,  USA,  and Japan . HCV subtype 3a is the most common genotype circulating in India , Nepal  and Pakistan . HCV genotype 4 prevailing in the Middle East and North Africa , and genotypes 5 and 6 appears to be most common to South Africa and Hong Kong, respectively . Genetic analysis of HCV genotype 3a is very important as it is very sensitive to interferon therapy compared to the other genotypes.
List of the hepatitis C virus genotype 3a sequences used in the analysis.
GenBank accession No.
2010-S52 (Synthetic construct)
Phylogenetic analysis of the isolate PK-1 and all the full length HCV genotype 3a genomes (n = 7) in the GenBank database (Table 1) by using MEGA4 software package. Two different methods (UPGMA method and Neighbor Joining (NJ) method) of the phylogenetic analysis were used as described previously . Evolutionary distances were also estimated by using methods previously reported by Tamura et al .
Estimates of evolutionary divergence between sequences with standard error estimates.
Sources of support: This work was partially supported by the Higher Education Commission of Pakistan.
- Poynard T, Ratziu V, Benhamou Y, Opolon P, Cacoub P, Bedossa P: Natural history of HCV infection. Best Pract Res Clin Gastroenterol. 2000, 14: 211-228. 10.1053/bega.1999.0071.View ArticleGoogle Scholar
- Butt S, Idrees M, Akbar H, Rehman I, Awan Z, Afzal S, et al: The changing epidemiology pattern and frequency distribution of hepatitis C virus in Pakistan. Infect Genet Evol. 2010, 10 (5): 595-600. 10.1016/j.meegid.2010.04.012.View ArticlePubMedGoogle Scholar
- Idrees M, Lal A, Naseem M, Khalid M: High prevalence of hepatitis C virus infection in the largest province of Pakistan. J Dig Dis. 2008, 9: 95-103. 10.1111/j.1751-2980.2008.00329.x.View ArticlePubMedGoogle Scholar
- Ogata N, Alter HJ, Miller RH, Purcell RH: Nucleotide sequence and mutation rate of the H strain of hepatitis C virus. Proc Natl Acad Sci USA. 1991, 88: 3392-3396. 10.1073/pnas.88.8.3392.PubMed CentralView ArticlePubMedGoogle Scholar
- Lemon SM, Walker CM, Alter MJ, Yi M: Fields Virology. 2007, Lippincot Williams and Wilkins, Philadelpia. Hepatitis C virus, 1253-1304.Google Scholar
- Dusheiko G, Main J, Thomas H: Ribavirin treatment for patients with chronic hepatitis C: results of a placebo-controlled study. Hepatology. 1994, 25: 591-598.View ArticleGoogle Scholar
- Zein NN, Persing DH: Hepatitis C Genotypes: current trends and future implications. Mayo Clin Proc. 1996, 71: 458-462. 10.4065/71.5.458.View ArticlePubMedGoogle Scholar
- Takada NS, Takase S, Takada A, Date T: Differences in the hepatitis C virus genotypes in different countries. J Hepatol. 1993, 17: 277-283. 10.1016/S0168-8278(05)80205-3.View ArticlePubMedGoogle Scholar
- Singh B, Verma M, Verma K: Markers for transfusion associated hepatitis in North Indian blood donors: prevalence and trends. Jpn J Infec Dis. 2004, 57: 49-51.Google Scholar
- Tokita H, Shrestha SM, Okamoto H, Sakamoto M, Horikita M, et al: Hepatitis C virus variants from Nepal with novel genotypes and their classification into the third major group. J Gen Virol. 1994, 75: 931-936. 10.1099/0022-1317-75-4-931.View ArticlePubMedGoogle Scholar
- Idrees M, Riazuddin S: Frequency distribution of hepatitis C virus genotypes in different geographical regions of Pakistan and their possible routes of transmission. BMC Infect Dis. 2008, 8: 69-10.1186/1471-2334-8-69.PubMed CentralView ArticlePubMedGoogle Scholar
- Abdulkarim AS, Zein NN, Germer JJ, Kolbert CP, Kabbani L, Krajnik KL: Hepatitis C virus genotypes and hepatitis G virus in hemodialysis patients from Syria: identification of two novel hepatitis C virus subtypes. Am J Trop Med Hyg. 1998, 59: 571-576.PubMedGoogle Scholar
- Simmonds P, Holmes EC, Cha TA, Chan SW, McOmish F, Irvine B: Classification of hepatitis C virus into six major genotypes and a series of subtypes by phylogenetic analysis of the NS-5 region. J Gen Virol. 1993, 74: 2391-2399. 10.1099/0022-1317-74-11-2391.View ArticlePubMedGoogle Scholar
- Bracho MA, Saludes V, Martro E, Bargallo A, González-Candelas F, Ausina V: Complete genome of a European hepatitis C virus subtype 1 g isolate: phylogenetic and genetic analyses. Virol J. 2008, 5: 72-10.1186/1743-422X-5-72.PubMed CentralView ArticlePubMedGoogle Scholar
- Chamberlain RW, Adams N, Saeed AA, Simmonds P, Elliott RM: Complete nucleotide sequence of a type 4 hepatitis C virus variant, the predominant genotype in the Middle East. J Gen Virol. 1997, 78: 1341-1347.View ArticlePubMedGoogle Scholar
- Tamura K, Dudley J, Nei M, Kumar S: MEGA4: Molecular Evolutionary Genetics Analysis (MEGA) software version 4.0. Mol Biol Evol. 2007, 24: 1596-1599. 10.1093/molbev/msm092.View ArticlePubMedGoogle Scholar
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